Confronting hidden COVID-19 burden: a telemedical solution for elective urological outpatient clinics

Maintaining high-quality care for urological patients is a challenge during and after the Coronavirus disease 2019 (COVID-19) pandemic. We observe an increasing volume of postponed elective visits at our tertiary care hospital, holding the risk for deterioration of non-emergency disease conditions. As it is unclear for how long the pandemic will last, we propose to implement telehealth as a solution to provide regular symptom monitoring compatible with social distancing guidelines during the pandemic and beyond. Telemedical assessment and prioritizing of high-risk patients for individual consults at outpatient services will have to be aligned with available outpatient capacity and local outbreak severity

Digital innovation in medicine: the COVID-19 pandemic as an accelerator of “digital health”

Die COVID-19-Pandemie hat eine Welle der Digitalisierung in der Medizin ausgelöst. Der Einsatz modernster Technologien wird in den folgenden Jahren Routinediagnostik und Therapieansätze revolutionieren und die Arzt-Patienten-Beziehung positiv beeinflussen. Die Verwendung von AI („artifical intelligence“) und Big Data ist neben den Entwicklungen der mHealth („mobile health“) einer der bedeutendsten Meilensteine im Aufbau eines digitalen und intelligenten Gesundheitssystems.The COVID-19 pandemic has triggered a wave of digitalization in medicine. In the coming years, the use of state-of-the-art technologies will revolutionize routine diagnostic and treatment approaches, as well as have a positive effect on the physician–patient relationship. The application of AI (artificial intelligence) and Big Data, combined with the development of mHealth (mobile health), represents the most significant milestone in the creation of a digital and intelligent health system

Digitale Innovation in der Medizin – die COVID-19-Pandemie als Akzelerator von „digital health“

The COVID-19 pandemic has triggered a wave of digitalization in medicine. In the coming years, the use of state-of-the-art technologies will revolutionize routine diagnostic and treatment approaches, as well as have a positive effect on the physician-patient relationship. The application of AI (artificial intelligence) and Big Data, combined with the development of mHealth (mobile health), represents the most significant milestone in the creation of a digital and intelligent health system!Die COVID-19-Pandemie hat eine Welle der Digitalisierung in der Medizin ausgelöst. Der Einsatz modernster Technologien wird in den folgenden Jahren Routinediagnostik und Therapieansätze revolutionieren und die Arzt-Patienten-Beziehung positiv beeinflussen. Die Verwendung von AI („artifical intelligence“) und Big Data ist neben den Entwicklungen der mHealth („mobile health“) einer der bedeutendsten Meilensteine im Aufbau eines digitalen und intelligenten Gesundheitssystems

Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value-Need for Biomarker Testing in High-Risk Patients?

Simple Summary Variant histologies of bladder cancer present at advanced stage and are often treated with radical cystectomy. As Nectin-4 appears to be a promising target for novel therapies in conventional bladder cancer, we aimed to analyze the expression of Nectin-4 and its prognostic value in variant histologies of bladder cancer. We found a high expression of Nectin-4 in squamous cell carcinoma and adenocarcinoma and a low expression in sarcomatoid urothelial carcinoma. No impact of Nectin-4 expression on survival has been detected in our study. Our study reveals the need to perform further biomarker testing for Nectin-4 in prospective trials including patients with variant histologies. Variant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as a highly interesting target in BC and might guide therapeutic application of antibody-drug conjugates (ADC). We therefore aimed to investigate expression patterns and prognostic value of Nectin-4 in variant histologies of BC. A single-center retrospective analysis was conducted of patients who underwent radical cystectomy (RC) for BC and revealed variant histologies of BC in the final specimens. Immunohistochemical staining for Nectin-4 was performed on tissue microarrays with 59 SCC, 22 ADENO, and 24 SARCO, and Nectin-4 expression was scored using the histochemical scoring system (H-score). Overall survival (OS) and progression-free survival (PFS) was calculated by Kaplan-Meier method. Median expression of Nectin-4 was 150 (range 0-250) in SCC, 140.5 (range 30-275) in ADENO, and 10 (0-185) in SARCO, with significantly lower levels for SARCO compared to SCC or ADENO (p 0.05). Multivariate analysis revealed nodal stage as an independent prognostic factor for OS and PFS and metastases for PFS but not Nectin-4 expression. In conclusion, Nectin-4 was not prognostic in histological subtypes of BC in our study cohort. However, the high expression of Nectin-4 in SCC and ADENO might guide future treatment with novel Nectin-4-directed ADCs and provide this high-risk patient collective with a new promising therapeutic option. Testing Nectin-4 expression as a biomarker should be considered in trials with SARCO, where low Nectin-4 expression has been observed

Identification of the Tumor Infiltrating Lymphocytes (TILs) Landscape in Pure Squamous Cell Carcinoma of the Bladder

Simple Summary Treatment options in squamous cell carcinoma (SCC) of the bladder are limited and prognosis is poor. In this report we investigated the impact of tumor-infiltrating lymphocytes (TILs) in SCC of the bladder in patients undergoing radical cystectomy. We found that subsets of TILs hold predictive value for OS and PFS. We conclude that TILs might stratify patients with bladder SCC for immunotherapy. Background: Tumor infiltrating lymphocytes (TILs) are known as important prognostic biomarkers and build the fundament for immunotherapy. However, the presence of TILs and its impact on outcome in pure squamous cell carcinoma (SCC) of the bladder remains uncertain. Methods: Out of 1600 patients undergoing radical cystectomy, 61 patients revealed pure bladder SCC in the final histopathological specimen. Retrospectively, immunohistochemical staining was performed on a subset of TILs (CD3+, CD4+, CD8+, CD20+). Endpoints were overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). The Kaplan-Meier method was used to evaluate survival outcomes. Results: Strong infiltration of CD3+ was found in 27 (44%);of CD4+ in 28 (46%);of CD8+ in 26 (43%);and of CD20+ in 27 tumors (44%). Improved OS was observed for strong CD3+ (p < 0.001);CD4+ (p = 0.045);CD8+ (p = 0.001);and CD20+ infiltration (p < 0.001). Increased rates of PFS were observed for CD3+ (p = 0.025) and CD20+ TILs (p = 0.002). In multivariate analyses, strong CD3+ (HR: 0.163, CI: 0.044-0.614) and strong CD8+ TILs (HR: 0.265, CI: 0.081-0.864) were revealed as predictors for OS and the strong infiltration of CD20+ cells (HR: 0.095, CI: 0.019-0.464) for PFS. Conclusions: These first results of TILs in bladder SCC revealed predictive values of CD3+, CD8+ and CD20+

IL-22 sustains epithelial integrity in progressive kidney remodeling and fibrosis

IL-22, a member of the IL-10 cytokine family, accelerates tubule regeneration upon acute kidney injury, hence we speculated on a protective role also in chronic kidney disease. We quantified intrarenal IL-22 expression after unilateral ureteral (UUO) in wild-type mice and performed UUO in IL-22 knock-out animals. Obstruction phenotypic differences between IL22(+/+) and IL22(-/-) mice were assessed by histology, immunohistochemistry, immunofluorescence as well as western blotting and reverse-transcriptase quantitative PCR ex vivo. Additionally, we performed in vitro experiments using both murine and human tubular cells to characterize IL-22 effects in epithelial healing. We found increasing IL22 positivity in infiltrating immune cells over time upon UUO in wild-type mice. UUO in IL22(-/-) mice caused more tubular cell injury as defined by TUNEL positive cells and loss of tetragonolobus lectin staining. Instead, tubular dilation, loss of CD31+ perivascular capillaries, and interstitial fibrosis were independent of the Il22 genotype as assessed by standard histology, immunostaining, and mRNA expression profiling. In vitro experiments showed that recombinant human IL-22 significantly enhanced human tubular epithelial cell proliferation and wound closure upon mechanical injury, and electric cell-substrate impedance sensing studies revealed that recombinant IL-22 sustained tubular epithelial barrier function upon injury. In contrast, IL-22 had no such direct effects on human fibroblasts. Together, in progressive kidney remodeling upon UUO, infiltrating immune cells secrete IL-22, which augments tubular epithelial integrity and epithelial barrier function, but does not affect vascular rarefaction or fibrogenesis. We conclude that IL-22 could represent a molecular target to specifically modulate tubular atrophy

68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results

BACKGROUND 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. RESULTS Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. CONCLUSION Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients